PONE-D-23-42882Efficacy of Zinc Fortified and Fermented Wheat Flour: A Randomized Controlled Trial ProtocolPLOS ONE

Dear Dr. Das,

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PLOS ONE

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Additional Editor Comments:

Dear Authors

According the remarks of both reviewers minor revisions must be implemented in your manuscript.

Please take into account all the comments in order to proceed to final stage of the publication process.

Best regards

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the opportunity to review this paper. This is an interesting manuscript presenting a protocol of a randomized controlled tral on effecacy of Zinc Fortified and fermented wheat flour. My review mainly concerns only the statistical aspects of the study. Some questions reported below were raised and in my view, it is not acceptable in this form for the publication in this journal.The "trial analysis" paragraph should be more detailed. Particularly in relation to multivariate models. Authors should anticipate Intention-to-treat analysis of the missing data and possible sensitivity analyses.

Reviewer #2: Upon reviewing the manuscript titled "Efficacy of Zinc Fortified and Fermented Wheat Flour (EZAFFAW): A Randomized Controlled Trial Protocol" (Manuscript Number: PONE-D-23-42882), it became evident that the authors have outlined a comprehensive and timely protocol that addresses the urgent need of developing strategies to mitigate zinc deficiency among the population, particularly adolescent and young women living in economically disadvantages areas. The proposed protocol includes 1000 participants, allocated by stratified randomization to four groups. Zn supplementation of the daily diet via its incorporation into bread, a common food for the population appears to be a promising option.

Monitoring the impacts on morbidity, anthropometric and biochemical indicators, and other key metrics is ensured through the evaluation of multiple indicators.

The processes for obtaining flour that has been fortified with ZnO or biofortified via foliar spraying with ZnSO4.7H2O is comprehensively elucidated, along with the process of bread preparation. Nonetheless, I would like to pose a few questions:

1. Why was not the same variety of wheat used for the production of both agronomically biofortified and biofortified flour?

2. During the preparation of the bread, the dough was left to rest for 30 minutes or more (depending on whether it was fermented or not) at what temperature?

7. In the section "Data analysis - Food testing" the quantification of phytate includes a stirring period of 3 hours. Regarding the technique and temperature involved, I propose that it be clarified more deeply.

********** 

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Reviewer #1: No

Reviewer #2: No

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Efficacy of Zinc Fortified and Fermented Wheat Flour: A Randomized Controlled Trial Protocol

PONE-D-23-42882R1

Dear Dr. Das,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Fernando Henrique da Silva Reboredo, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Thank you to the authors for including the recommended suggestions.

After receiving clear explanations for my questions, I believe that the paper is now suitable for publication.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

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